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Renal cell carcinoma (RCC) represents 2% of all diagnosed malignancies worldwide, with disease recurrence affecting 20% to 40% of patients. Existing prognostic recurrence models based on clinicopathological features continue to be a subject of controversy. In this meta-analysis, we summarized research findings that explored the correlation between clinicopathological characteristics and post-surgery survival outcomes in non-metastatic RCC patients. Our analysis incorporates 99 publications spanning 140 568 patients. The study's main findings indicate that the following clinicopathological characteristics were associated with unfavorable survival outcomes: T stage, tumor grade, tumor size, lymph node involvement, tumor necrosis, sarcomatoid features, positive surgical margins (PSM), lymphovascular invasion (LVI), early recurrence, constitutional symptoms, poor performance status (PS), low hemoglobin level, high body-mass index (BMI), diabetes mellitus (DM) and hypertension. All of which emerged as predictors for poor recurrence-free survival (RFS) and cancer-specific survival. Clear cell (CC) subtype, urinary collecting system invasion (UCSI), capsular penetration, perinephric fat invasion, renal vein invasion (RVI) and increased C-reactive protein (CRP) were all associated with poor RFS. In contrast, age, sex, tumor laterality, nephrectomy type and approach had no impact on survival outcomes. As part of an additional analysis, we attempted to assess the association between these characteristics and late recurrences (relapses occurring more than 5 years after surgery). Nevertheless, we did not find any prediction capabilities for late disease recurrences among any of the features examined. Our findings highlight the prognostic significance of various clinicopathological characteristics potentially aiding in the identification of high-risk RCC patients and enhancing the development of more precise prediction models.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Rim/patologia , Prognóstico , Nefrectomia , Estudos Retrospectivos , Estadiamento de NeoplasiasRESUMO
OBJECTIVES: To determine and summarize the available data on urinary, sexual, and health-related quality-of-life (HRQOL) outcomes after traditional radical cystectomy (RC), reproductive organ-preserving RC (ROPRC) and nerve-sparing RC (NSRC) for bladder cancer (BCa) in female patients. METHODS: The PubMed, SCOPUS and Web of Science databases were searched to identify studies reporting functional outcomes in female patients undergoing RC and urinary diversion for the treatment of BCa. The outcomes of interest were voiding function (for orthotopic neobladder [ONB]), sexual function and HRQOL. The following independent variables were derived and included in the meta-analysis: pooled rate of daytime and nighttime continence/incontinence, and intermittent self-catheterization (ISC) rates. Analyses were performed separately for traditional, organ- and/or nerve-sparing surgical approaches. RESULTS: Fifty-three studies comprising 2740 female patients (1201 traditional RC and 1539 organ-/nerve-sparing RC, and 264 nerve-sparing-alone RC) were eligible for qualitative synthesis; 44 studies comprising 2418 female patients were included in the quantitative synthesis. In women with ONB diversion, the pooled rates of daytime continence after traditional RC, ROPRC and NSRC were 75.2%, 79.3% and 71.2%, respectively. The pooled rate of nighttime continence after traditional RC was 59.5%; this rate increased to 70.7% and 71.7% in women who underwent ROPRC and NSRC, respectively. The pooled rate of ISC after traditional RC with ONB diversion in female patients was 27.6% and decreased to 20.6% and 16.8% in patients undergoing ROPRC and NSRC, respectively. The use of different definitions and questionnaires in the assessment of postoperative sexual and HRQOL outcomes did not allow a systematic comparison. CONCLUSIONS: Female organ- and nerve-sparing surgical approaches during RC seem to result in improved voiding function. There is a significant need for well-designed studies exploring sexual and HRQOL outcomes to establish evidence-based management strategies to support a shared decision-making process tailored towards patient expectations and satisfaction. Understanding expected functional, sexual and quality-of-life outcomes is necessary to allow individualized pre- and postoperative counselling and care delivery in female patients planned to undergo RC.
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Neoplasias da Bexiga Urinária , Derivação Urinária , Incontinência Urinária , Humanos , Feminino , Cistectomia/efeitos adversos , Bexiga Urinária/cirurgia , Incontinência Urinária/epidemiologia , Incontinência Urinária/etiologia , Incontinência Urinária/prevenção & controle , Micção , Derivação Urinária/efeitos adversos , Resultado do TratamentoRESUMO
PURPOSE: There are limited pooled data showing the impact of visceral metastasis on oncologic outcomes in metastatic prostate cancer patients treated with combination systemic therapies. We aimed to analyze and compare the efficacy of combination systemic therapies in metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer with or without visceral metastasis. MATERIALS AND METHODS: Three databases were queried in July 2022 for randomized, controlled trials analyzing metastatic prostate cancer patients treated with combination systemic therapy (androgen receptor signaling inhibitor and/or docetaxel plus androgen deprivation therapy) to standard of care. We analyzed the association between presence of visceral metastases and efficacy of systemic therapies in metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer patients. The main and secondary outcomes of interest were overall survival and progression-free survival, respectively. Formal meta-analysis using fixed-effect model and network meta-analysis using random-effect model were conducted. We followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) and AMSTAR (A MeaSurement Tool to Assess systematic Reviews) guidelines. RESULTS: Overall, 12 and 8 randomized, controlled trials were included for systematic review and meta-analyses/network meta-analyses, respectively. In metastatic hormone-sensitive prostate cancer patients, adding androgen receptor signaling inhibitor to standard of care improved overall survival in patients with visceral metastasis (pooled HR: 0.77, 95% CI: 0.64-0.94) as well as in those without (pooled HR: 0.66, 95% CI: 0.60-0.72; no differences in both across- and within-trial approach; P = .13 and P = .06, respectively). On the other hand, the progression-free survival benefit from androgen receptor signaling inhibitor + androgen deprivation therapy was significantly lower in patients with visceral metastasis using across-trial approach (P = .03), while it did not reach statistical significance using within-trial approach (P = .14). Analysis of treatment ranking in metastatic hormone-sensitive prostate cancer showed that darolutamide + docetaxel + androgen deprivation therapy had the highest likelihood of improved overall survival irrespective of visceral metastasis. In post-docetaxel metastatic castration-resistant prostate cancer patients, adding androgen receptor signaling inhibitor to androgen deprivation therapy significantly improved overall survival in both patients with visceral metastasis (pooled HR: 0.79, 95% CI: 0.63-0.98) and those without (pooled HR: 0.63, 95% CI: 0.55-0.72). No randomized, controlled trials reported the differential oncologic outcomes stratified by lung vs liver metastases. CONCLUSIONS: Despite aggressive clinical behavior and worse trajectory of metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer with visceral metastasis, the effectiveness of novel systemic therapies is similar in both metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer patients with and without visceral metastasis. Further well-designed studies with detailed visceral metastatic sites and number will enrich the clinical decision-making.
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Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Docetaxel , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Metanálise em Rede , Antagonistas de Androgênios , Receptores Androgênicos , Androgênios/uso terapêutico , Antagonistas de Receptores de Andrógenos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Metástase NeoplásicaRESUMO
OBJECTIVE: To assess the association between cystoscopic findings and oncological outcomes in patients with non-muscle-invasive bladder cancer (NMIBC) given that the oncological impact of quantity and quality assessment of tumours with cystoscopy has not been well verified. METHODS: Multiple databases were queried in May 2022 for studies investigating the association of oncological outcomes, such as recurrence-free (RFS), progression-free (PFS), and cancer-specific survival (CSS), with cystoscopic findings, including multiplicity, size, and gross appearance of tumours in patients with NMIBC. RESULTS: Overall, 73 studies comprising 28 139 patients were eligible for the meta-analysis. Tumour multiplicity was associated with worse RFS (pooled hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.48-1.74) and PFS (pooled HR 1.44, 95% CI 1.18-1.76) in NMIBC patients (including both Ta and T1). Tumour size (≥3 cm) was associated with worse RFS (pooled HR 1.97, 95% CI 1.69-2.30) and PFS (pooled HR 1.81, 95% CI 1.52-2.15) in NMIBC patients. In patients with T1 bladder cancer (BCa), tumour multiplicity and size (≥3 cm) were also associated with worse RFS, PFS and CSS. By contrast, among patients treated with bacillus Calmette-Guérin (BCG), tumour multiplicity was not associated with worse RFS, and tumour size (≥3 cm) was not associated with worse PFS. Sessile tumours were associated with worse RFS (pooled HR 2.14, 95% CI 1.52-3.01) and PFS (pooled HR 2.17, 95% CI 1.42-3.32) compared to pedunculated tumours. Compared to papillary tumours, solid tumours were associated with worse RFS (pooled HR 1.84, 95% CI 1.25-2.72) and PFS (pooled HR 3.06, 95% CI 2.31-4.07) in NMIBC patients, and CSS in T1 BCa patients (pooled HR 2.32, 95% CI 1.63-3.30). CONCLUSIONS: Cystoscopic findings, including tumour multiplicity, size, and gross appearance, strongly predict oncological outcomes in NMIBC patients. Cystoscopic visual features can help in the decision-making process regarding the timeliness and extent of tumour resection as well as future management such as intravesical therapy.
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Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/patologia , Modelos de Riscos Proporcionais , Cistoscopia , Vacina BCG/uso terapêutico , Administração Intravesical , Recidiva Local de Neoplasia/patologia , Invasividade Neoplásica , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the efficacy of systemic therapies in patients with worse performance status (PS) treated for high-risk non-metastatic prostate cancer (PCa), metastatic hormone-sensitive PCa (mHSPC), and non-metastatic/metastatic castration-resistant PCa (nmCRPC/mCRPC), as there is sparse pooled data showing the effect of PS on oncological outcomes in patients with PCa. METHODS: Three databases were queried in June 2022 for randomised controlled trials (RCTs) analysing patients with PCa treated with systemic therapy (i.e., adding androgen receptor signalling inhibitor [ARSI] or docetaxel [DOC] to androgen-deprivation therapy [ADT]). We analysed the oncological outcomes of patients with PCa with worse PS, defined as Eastern Cooperative Oncology Group PS ≥ 1, treated with combination therapies and compared these to patients with good PS. The main outcomes of interest were overall survival (OS), metastasis-free survival (MFS), and progression-free survival. RESULTS: Overall, 25 and 18 RCTs were included for systematic review and meta-analyses/network meta-analyses, respectively. In all clinical settings, combination systemic therapies significantly improved OS in patients with worse PS as well as in those with good PS, while the MFS benefit from ARSI in the nmCRPC setting was more pronounced in patients with good PS than in those with worse PS (P = 0.002). Analysis of treatment ranking in patients with mHSPC revealed that triplet therapy had the highest likelihood of improved OS irrespective of PS; specifically, adding darolutamide to DOC + ADT had the highest likelihood of improved OS in patients with worse PS. Analyses were limited by the small proportion of patients with a PS ≥ 1 (19%-28%) and that the number of PS 2 was rarely reported. CONCLUSIONS: Among RCTs, novel systemic therapies seem to benefit the OS of patients with PCa irrespective of PS. Our findings suggest that worse PS should not discourage treatment intensification across all disease stages.
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Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Docetaxel/uso terapêutico , Antagonistas de Androgênios/efeitos adversos , Intervalo Livre de Progressão , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
PURPOSE: To analyze and summarize the efficacy of immune checkpoint inhibitor (ICI) alone or in combination therapy for renal cell carcinoma (RCC) and urothelial carcinoma (UC) stratified by sex. METHODS: Three databases were queried in October 2022 for randomized controlled trials (RCTs) analyzing RCC and UC patients treated with ICIs. We analyzed the association between sex and the efficacy of ICIs in RCC and UC patients across several clinical settings. The outcomes of interest were overall survival (OS) and progression-free survival for the metastatic setting and disease-free survival (DFS) for the adjuvant setting. RESULTS: Overall, 16 RCTs were included for meta-analyses and network meta-analyses. In the first-line treatment of metastatic RCC (mRCC) and UC (mUC) patients, ICI-based combination therapies significantly improved OS compared to the current standard of care, regardless of sex. Adjuvant ICI monotherapy reduced the risk of disease recurrence in female patients with locally advanced RCC (pooled hazard ratio [HR]: 0.71, 95% confidence interval [CI] 0.55-0.93) but not in male patients, and, conversely, in male patients with muscle-invasive UC (pooled HR: 0.80, 95%CI 0.68-0.94) but not in female patients. Treatment ranking analyses in the first-line treatment of mRCC and mUC showed different results between sexes. Of note, regarding adjuvant treatment for RCC, pembrolizumab (99%) had the highest likelihood of improved DFS in males, whereas atezolizumab (84%) in females. CONCLUSIONS: OS benefit of first-line ICI-based combination therapy was seen in mRCC and mUC patients regardless of sex. Sex-based recommendations for ICI-based regimens according to the clinical setting may help guide clinical decision-making.
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Carcinoma de Células Renais , Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias da Bexiga Urinária , Feminino , Masculino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Recidiva Local de Neoplasia , Carcinoma de Células de Transição/tratamento farmacológico , Rim , Adjuvantes Imunológicos , Neoplasias Renais/tratamento farmacológicoRESUMO
PURPOSE: To evaluate the prognostic value and the clinical impact of preoperative serum cholinesterase (ChoE) levels on decision-making in patients treated with radical nephroureterectomy (RNU) for clinically non-metastatic upper tract urothelial cancer (UTUC). METHODS: A retrospective review of an established multi-institutional UTUC database was performed. We evaluated preoperative ChoE as a continuous and dichotomized variable using a visual assessment of the functional form of the association of ChoE with cancer-specific survival (CSS). We used univariable and multivariable Cox regression models to establish its association with recurrence-free survival (RFS), CSS, and overall survival (OS). Discrimination was evaluated using Harrell's concordance index. Decision curve analysis (DCA) was used to assess the impact on clinical decision-making of preoperative ChoE. RESULTS: A total of 748 patients were available for analysis. Within a median follow-up of 34 months (IQR 15-64), 191 patients experienced disease recurrence, and 257 died, with 165 dying of UTUC. The optimal ChoE cutoff identified was 5.8 U/l. ChoE as continuous variable was significantly associated with RFS (p < 0.001), OS (p < 0.001), and CSS (p < 0.001) on univariable and multivariable analyses. The concordance index improved by 8%, 4.4%, and 7% for RFS, OS, and CSS, respectively. On DCA, including ChoE did not improve the net benefit of standard prognostic models. CONCLUSION: Despite its independent association with RFS, OS, and CSS, preoperative serum ChoE has no impact on clinical decision-making. In future studies, ChoE should be investigated as part of the tumor microenvironment and assessed as part of predictive and prognostic models, specifically in the setting of immune checkpoint-inhibitor therapy.
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Carcinoma de Células de Transição , Sistema Urinário , Neoplasias Urológicas , Humanos , Nefroureterectomia , Colinesterases , Recidiva Local de Neoplasia/cirurgia , Neoplasias Urológicas/patologia , Prognóstico , Carcinoma de Células de Transição/patologia , Estudos Retrospectivos , Microambiente TumoralRESUMO
Nowadays, there is confusing evidence in the literature regarding the association between seasonal variations and events of testicular torsion (TT). We attempted to assess the correlation between seasonal variations, including season, ambient temperatures, and humidity levels to onset and laterality of testicular torsion. We conducted a retrospective review of patients diagnosed with testicular torsion and confirmed surgically between January 2009 and December 2019, at Hillel Yaffe Medical Center. Weather data was collected from meteorological observation stations near the hospital. TT incidents were stratified into five temperature categories (< 15 °C, 15-20 °C, 20-25 °C, 25-30 °C, > 30 °C) and into two categories of humidity (≤ 50%, > 50%). Potential associations between TT and seasonal variations were investigated. Of 235 patients diagnosed with TT, 156 (66%) were children and adolescents and 79 (34%) were adults. In both groups, rate of TT incidents increased in winter and fall months. Significant correlation between TT and temperatures below 15 °C was observed in both groups; OR 3.3 [95% IC 1.54-7.07], p = 0.002 in children and adolescents and 3.77 [1.79-7.94], p < 0.001) in adults. The correlation between TT and humidity was non-significant in both groups. Among children and adolescents left-sided TT was observed in most of the cases, with strong correlation to lower temperatures; OR 3.15 [1.34-7.40], p = 0.008. Higher rates of acute TT were observed in patients admitted to the emergency department (ED) during the cold seasons in Israel. Significant association was observed between left-side TT and temperatures below 15 °C in the children and adolescents' group. Our findings suggest that there might be a predilection for TT occurrence in cold weather, particularly left-side laterality among children and adolescents.
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Torção do Cordão Espermático , Masculino , Criança , Adulto , Adolescente , Humanos , Estações do Ano , Torção do Cordão Espermático/epidemiologia , Torção do Cordão Espermático/diagnóstico , Torção do Cordão Espermático/etiologia , Incidência , Tempo (Meteorologia) , Temperatura Baixa , Estudos RetrospectivosRESUMO
Hydrocele is a common benign scrotal condition affecting adult men. The gold standard of treatment includes hydrocelectomy, with the use of Winkelman's/Jaboulay's technique or Lord's procedure. The vessel-sealing device (VSD) is a blood vessel-sealing system, known to enhance patient's postoperative outcomes in multiple different surgeries. The aim of this study was to compare the procedural and postoperative outcomes of a novel hydrocelectomy method using a VSD to the conventional hydrocelectomy using the Jaboulay's technique. We performed A retrospective review for all adult cases who underwent surgical hydrocelectomy at Hillel Yaffe Medical Center between 2011 and 2022. Study cases were grouped into one of two groups, patients undergoing conventional hydrocelectomy, or patients undergoing hydrocelectomy with the use of a VSD. Patients operated using other techniques were excluded. Data collected included demographic data and operative and postoperative parameters. Among 102 patients, 47 underwent Jaboulay's technique and 55 underwent hydrocelectomy using a VSD. We observed significantly shorter duration of hospitalization (1.18 vs 1.53, P = 0.038) and shorter surgery time (31.87 vs 37.4, P = 0.003) when using the VSD during a hydrocelectomy compared to conventional surgical hydrocelectomy. Both techniques indicated low complication rates and no recurrent hydrocele was observed in either group. We report our experience with a novel surgical technique that includes hydrocelectomy with the use of VSD. Our findings demonstrated shorter surgery time and length of hospitalizations, which may indicate improved patient's postoperative outcomes with the use of the VSD for hydrocelectomy.
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OBJECTIVE: The impact of Ramadan fasting on the prevalence of renal colic (RC) remains controversial. This current study aimed to assess the correlation between Ramadan fasting, prevalence of RC and the rate of urgent endoscopic interventions due to urolithiasis. METHODS: This retrospective case-control study enrolled adult patients with a primary diagnosis of RC secondary to urolithiasis admitted to the emergency department during the years 2009-2019. The prevalence of RC and the rate of urgent urological interventions during Ramadan were compared with the pre- and post-Ramadan months in fasting Muslims and non-fasting non-Muslim patients. RESULTS: A total of 2781 patients with RC were included: 1014 (36.5%) were fasting Muslim and 1767 (63.5%) were non-fasting non-Muslim patients. No significant increase in RC admissions or urgent double J stent (DJS) insertions were observed between pre-Ramadan and Ramadan among fasting Muslims and non-fasting non-Muslim patients. However, fasting Muslims exhibited a significant increase of RC admissions post-Ramadan compared with Ramadan. CONCLUSIONS: There was no correlation between increased RC admissions or urgent DJS insertions when fasting Muslims were compared with non-fasting non-Muslim patients during Ramadan. There were increased RC admissions during the post-Ramadan month, which might indicate a delayed effect of fasting on RC.
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Jejum , Islamismo , Cólica Renal , Urolitíase , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Cólica Renal/epidemiologia , Cólica Renal/etiologia , Urolitíase/epidemiologia , Estudos de Casos e Controles , Adulto , Prevalência , Idoso , Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitalização/estatística & dados numéricosRESUMO
Urothelial tumors in patients with anatomical abnormalities may pose significant challenges. Management follows the same principles which are employed in normal anatomy, however, thorough diagnostic investigation is warranted in order to delineate key anatomical landmarks. Meticulous pre-operative investigation should utilize every imaging modality which can assist the surgeons. We present a case of transitional cell carcinoma (TCC) in a crossed-fused kidney treated with nephro-ureterectomy. Only a handful of cases of TCC in CFRE have been reported. The case demonstrates the critical role of pre-operative anatomical studies and intra-operative identification of unique anatomy, which facilitate treatment and avoid complications.
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OBJECTIVE: To investigate the impact of preoperative double J (DJ) stent insertion on outcomes of retrograde semi-rigid ureteroscopy (URS) in patients with upper small and medium sized ureteral stones. METHODS: Between April 2018 and September 2019, we retrospectively reviewed the medical register of Hillel Yaffe tertiary reference Centre (HYMC) for patients who had undergone retrograde semi-rigid URS for urolithiasis. Patients were separated into two groups depending on whether they accepted the DJ stent placement before URS (Group A) or not (Group B). Operating time, stone clearance rate, number of 'rescue' DJ stents, duration of 'rescue' stents, complication rate and requirement for repeat URS were compared between groups. RESULTS: 318 procedures undertaken in 290 patients were included (Group A, 83 procedures in 80 patiants; Group B, 235 procedures in 210 patients). By comparison with the non-stented group, patients in the preoperative DJ stented group had a higher stone clearance rate, lower complication rate, less need for postoperative 'rescue' DJ stent, lower duration of 'rescue' stent and lower re-operative URS requirement, including application of a flexible URS. CONCLUSION: Facilitated semi-rigid URS with upstream DJ stenting for small and medium size ureteral stones has favourable periprocedural outcomes compared with primary URS.
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Ureter , Cálculos Ureterais , Humanos , Ureteroscopia/métodos , Estudos Retrospectivos , Cálculos Ureterais/cirurgia , Cálculos Ureterais/complicações , Resultado do Tratamento , Ureter/cirurgiaRESUMO
Given the morbidity associated with radical cystectomy (RC) and the significant survival benefit for patients who experience tumor downstaging after neoadjuvant chemotherapy (NAC), there is growing interest in bladder preservation strategies for select patients who have a complete response (CR) to NAC. In this mini-review we discuss the concept of avoiding RC as an alternative option for patients who experience a clinical CR following NAC. Several studies support this concept, with comparable long-term survival outcomes observed for patients with cT0 disease after NAC and patients undergoing RC. However, the definitive approach and the optimal surveillance strategy for patients with a clinical CR who choose bladder preservation are lacking. A dynamic response-driven bladder preservation strategy is a highly anticipated option for patients and is needed to avoid debilitating overtreatment. PATIENT SUMMARY: For selected patients with bladder cancer who experience a complete response to chemotherapy before any surgery, close follow-up might be an alternative option to surgical removal of the bladder without compromising cancer control.
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Neoplasias da Bexiga Urinária , Bexiga Urinária , Humanos , Bexiga Urinária/cirurgia , Bexiga Urinária/patologia , Terapia Neoadjuvante , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Cistectomia/efeitos adversos , Resposta Patológica CompletaRESUMO
INTRODUCTION: Despite recent developments in the landscape of urothelial carcinoma (UC) treatment, platinum combination chemotherapy still remains a milestone. Recently immunotherapeutic agents have gained ever-growing attractivity, particularly in the metastatic setting. Novel chemotherapeutic strategies and agents, such as antibody-drug conjugates (ADCs), and powerful combination regimens have been developed to overcome the resistance of most UC to current therapies. AREAS COVERED: Herein, we review the current standard-of-care chemotherapy, the development of ADCs, the rationale for combining therapy regimens with chemotherapy in current trials, and future directions in UC management. EXPERT OPINION: Immunotherapy has prompted a revolution in the treatment paradigm of UC. However, only a few patients experience a long-term response when treated with single-agent immunotherapies. Combination treatments are necessary to bypass resistance mechanisms and broaden the clinical utility of current options. Current evidence supports the intensification of standard-of-care chemotherapy with maintenance immunotherapy. However, the optimal sequence, combination, and duration must be determined to achieve individual longevity with acceptable health-related quality of life. In that regard, ADCs appear as a promising alternative for single and combination strategies in UC, as they specifically target the tumor cells, thereby, theoretically improving treatment efficacy and avoiding extensive off-target toxicities.
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Antineoplásicos , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Qualidade de Vida , Antineoplásicos/uso terapêutico , ImunoterapiaRESUMO
The aim of this study was to identify and summarize available data on oncologic and safety outcomes for retrograde versus antegrade endoscopic surgery in patients with upper tract urothelial carcinoma (UTUC). We systematically searched studies reporting on endoscopic surgery in patients with UTUC. The primary outcome of interest was oncologic control, including bladder and upper urinary tract recurrences. The secondary outcomes were any-grade and major complications. Twenty studies comprising 1091 patients were included in our analysis. The pooled bladder recurrence rate was 35% (95% confidence interval [CI] 28.0-42.3%; I2 = 48%) after retrograde endoscopic surgery and 17.7% (95% CI 6.5-32.1%; I2 = 29%) after antegrade endoscopic surgery. The pooled upper urinary tract recurrence rate was 56.4% (95% CI 41.2-70.9; I2 = 93%) after retrograde endoscopic surgery and 36.2% (95% CI 25.5-47.6%; I2 = 57%) after antegrade endoscopic surgery. The pooled complication rate was 12.5% (95% CI 0.8-32.8%; I2 = 94%) for any-grade complications and 6.6% (95% CI 0.1-19.1%; I2 = 89%) for major complications in the retrograde endoscopic cohort. In summary, our analyses suggest promising oncologic benefits of antegrade kidney-sparing surgery in terms of bladder and upper urinary tract recurrence rates in UTUC. Retrograde endoscopic surgery is a safe procedure with a minimal risk of complications and acceptable oncologic outcomes. Research should address the hypothesis that endoscopic antegrade surgery can be a safe and effective alternative for well-selected patients. PATIENT SUMMARY: One of the surgical options for treatment of cancer of the upper urinary tract is removal of the tumor through a small telescope called an endoscope. The endoscope can be inserted via the urethra (called a retrograde approach) or through a small incision in the skin (antegrade approach). Our review shows that the antegrade approach seems to provide acceptable cancer control rates. Further research could help to identify the role for endoscope surgery in cancer of the upper urinary tract.
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Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/cirurgia , Carcinoma de Células de Transição/patologia , Ureteroscopia/efeitos adversos , Ureteroscopia/métodos , Neoplasias Ureterais/cirurgia , Neoplasias Ureterais/patologia , Neoplasias Renais/cirurgia , Neoplasias Renais/patologiaRESUMO
(1) Background: Local therapy is highly promising in a multimodal approach strategy for patients with low-volume metastatic prostate cancer (mPCa). We aimed to systematically assess and summarize the safety, oncologic, and functional outcomes of cytoreductive prostatectomy (cRP) in mPCa. (2) Methods: Three databases were queried in September 2022 for publications that analyzed mPCa patients treated with cytoreductive prostatectomy without restrictions. The outcomes of interest were progression-free survival (PFS), cancer-specific survival (CSS), overall survival (OS), perioperative complication rates, and functional outcomes following cRP. (3) Results: Overall, 26 studies were included in this systematic review. Among eight population-based studies, cRP was associated with a reduced risk of CSS and OS compared with no local therapy (NLT) after adjusting for the effects of possible confounders. Furthermore, one population-based study showed that cRP reduced the risk of CSS even when compared with radiotherapy (RT) of the prostate after adjusting for the effects of possible confounders. In addition, one randomized controlled trial (RCT) demonstrated that local therapy (comprising 85% of cRP) significantly improved the prostate-specific antigen (PSA)-PFS and OS. Overall, cRP had acceptable perioperative complication rates and functional outcomes. (4) Conclusions: Mounting evidence suggests that cRP offers promising oncological and functional outcomes and technical feasibility and that it is associated with limited complications. Well-designed RCTs that limit selection bias in patients treated with cRP are warranted.
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Procedimentos Cirúrgicos de Citorredução , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/terapia , Prostatectomia , Antígeno Prostático EspecíficoRESUMO
CONTEXT: The ablative effect of intravesical therapy is known for decades. However, the clinical feasibility and efficacy of chemoablation for non-muscle-invasive bladder cancer (NMIBC) have not become accepted. OBJECTIVE: To assess the treatment outcomes of chemoablation for NMIBC and to compare its safety with that of the standard treatment, transurethral resection of bladder tumors (TURBT) followed by intravesical therapy. EVIDENCE ACQUISITION: Multiple databases were queried in July 2022 for studies investigating the complete response (CR) rates and adverse events in NMIBC patients treated with chemoablation using mitomycin C (MMC), gemcitabine, epirubicin, or bacillus Calmette-Guérin. EVIDENCE SYNTHESIS: Overall, 23 studies comprising 1199 patients were eligible for this meta-analysis. Among these studies, 20 assessed the efficacy of chemoablation and three compared the treatment outcomes of MMC chemoablation versus standard treatment. Among patients treated with weekly administration of any agent, the pooled CR rates at initial assessment were 50.9% (95% confidence interval [CI]: 45.9-55.9) for the marker lesion and 47.5% (95% CI: 36.5-58.7) for well-selected NMIBC (ie, small tumors and/or a small number of tumors). Novel regimens for chemoablation such as MMC-gel (70.6%, 95% CI: 60.1-79.3) and an intensive MMC regimen (64.7%, 95% CI: 56.2-72.3) provided better CR rates in well-selected NMIBC patients. Comparable CR rates were noted irrespective of tumor multiplicity, whereas tumor size <5 mm was associated with a higher CR rate than tumor size ≥5 mm (odds ratio: 0.36, 95% CI: 0.17-0.79). The novel intensive MMC regimen resulted in lower rates of dysuria and urinary frequency than standard treatment. CONCLUSIONS: Despite the lack of long-term outcomes, chemoablation appears to be a promising treatment option for well-selected NMIBC patients and can potentially help avoid unnecessary TURBT, specifically in some elderly patients with intermediate-risk NMIBC. Further well-designed studies with larger cohorts are necessary to address the differential tolerability and long-term anticancer efficacy of this resurging approach. PATIENT SUMMARY: Bladder instillation therapy has a potential ablative effect for well-selected non-muscle-invasive bladder cancer. This can lead to the omission of an unnecessary surgical treatment.
Assuntos
Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Idoso , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Mitomicina , Gencitabina , Administração IntravesicalRESUMO
INTRODUCTION: There is a persistent lack of validated biomarkers that identify patients most likely to benefit from neoadjuvant chemotherapy (NAC) in urothelial carcinoma of the bladder (UCB). Therefore, the purpose of this study was to investigate the predictive and prognostic impact of the pretreatment neutrophil-to-lymphocyte ratio (NLR) in UCB patients treated with NAC and radical cystectomy (RC). PATIENTS AND METHODS: We conducted a retrospective analysis of an international-multicenter database comprising 404 UCB patients staged cT2-4N0-3M0. The cohort was split into low and high NLR using an optimal cutoff value determined by maximizing Youden's index. Logistic and Cox regression analyses were performed with respect to several clinical endpoints. The discriminative ability of the models and the additive discriminative value of NLR was assessed by calculating the area under receiver operating characteristics curves, C-index, and decision curve analysis (DCA). RESULTS: A total of 169 patients (41.8%) had a high NLR, which was associated with a decreased probability of complete response (CR, OR: 0.24 [95% CI, 0.13-0.42], P < .001) and/or partial response (PR, OR: 0.33 [95% CI, 0.21-0.49], P < .001). Adding the NLR to predictive reference models significantly improved their accuracy for the prediction of both CR and PR. A high NLR was associated with poor survival outcomes in the pretreatment setting, however, it didn't meaningfully change the C-index based on the model. CONCLUSION: We confirmed that an elevated NLR is an independent and clinically significant predictor of response to NAC and adverse pathological features in UCB treated with NAC plus RC. The accuracy of this biomarker in the age of immunotherapy warrants further evaluation.